The purpose of this research is to evaluate the behavioral significance of sprouting in the dentate gyrus (DG) of the hippocampal formation after uni- or bilateral lesions of the entorhinal cortex (EC) in rats. These studies will focus on the contribution that a proliferated homologous input (i.e., the crossed temporodentate projection) makes to the recovery from spatial alternation deficits associated with unilateral EC damage. Two criteria will be used to assess whether the sprouting is behaviorally meaningful: 1) The time course of the reinnervation must parallel the time course of the behavioral recovery. 2) Systematic manipulation of the sprouted fibers must produce a concomitant change in behavior. This investigation will employ two approaches to attain the stated objective: A) The difficulty of a learned alternation task will be varied to determine the limits within which sprouting in the DG contributes to behavioral recovery. B) Progressive lesions of the EC, which are known to accelerate DG sprouting, will be used to determine whether the rate of behavioral recovery is also accelerated. Spatial alternation will be used as the behavioral assay because previous evidence has shown it to be sensitive to the reinnervation of the DG after EC damage. The proposed project will provide fundamental new insights into a mechanism which potentially contributes to recovery of function after central nervous system injury.